Varenicline for Nicotine Addiction

(VR Trial)

Overseen By Norma Castro, MA

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of California, San Diego

Disqualifiers: Severe cardiovascular disease, Seizures, Others

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 8 days

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called varenicline (also known as Champix or Chantix) to help daily smokers reduce nicotine cravings and use. Participants will be randomly assigned to receive either varenicline or a placebo (a pill with no active drug) to compare effectiveness. The study uses a virtual reality system to measure reactions to smoking cues. It is suitable for individuals from the San Diego area who have smoked at least five cigarettes daily for the past three months and have a smoking history of more than three years. As an Early Phase 1 trial, this research focuses on understanding how varenicline works in people, offering participants a chance to contribute to groundbreaking insights.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have any conditions that are contraindicated with varenicline, you may not be eligible to participate.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that varenicline is generally safe for helping people quit smoking. Studies have found it more effective than a placebo, meaning people using varenicline are more likely to quit. Most people tolerate it well, though some might experience mild side effects like nausea. These side effects are usually less severe than those from other treatments. Many other studies have used varenicline safely, supporting its use in this trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for nicotine addiction, which often include nicotine replacement therapies like patches and gum or medications such as bupropion, varenicline tartrate works uniquely by targeting nicotine receptors in the brain. This action reduces cravings and withdrawal symptoms, offering a distinct mechanism of action compared to other options. Researchers are particularly excited about varenicline because it not only curbs the urge to smoke but also diminishes the pleasure derived from smoking, potentially increasing its effectiveness in helping people quit smoking. Additionally, its structured titration schedule allows for gradual acclimation to the medication, potentially reducing side effects and improving compliance.

What evidence suggests that varenicline might be an effective treatment for nicotine addiction?

In this trial, participants will be randomized to receive either varenicline or a placebo. Studies have shown that varenicline helps people quit smoking. Several clinical trials have proven varenicline to be a safe and effective method for smoking cessation. For example, one study found that 45% of people using varenicline quit smoking, a much higher rate than those not using it. Another trial showed that 24% of people using varenicline stopped smoking, compared to just 9% using other treatments. Overall, research suggests that varenicline often leads to better long-term success in quitting smoking compared to other methods. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for daily tobacco users aged 22 or older who smoke at least 5 cigarettes a day and have been doing so for over 3 years. Participants must be willing to follow the study procedures, take oral medication, and if they can become pregnant, use effective contraception.

Inclusion Criteria

I can take pills and will follow the medication schedule.

I have craved nicotine in the past week.

I am 22 years old or older.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants are assessed on the VR Nicotine Cue Exposure paradigm and randomized to receive varenicline or placebo

1 day

1 visit (in-person)

Titration

Participants undergo an 8-day titration period to reach the target dose of varenicline or placebo

8 days

1 visit (in-person) at the end of titration

Treatment

Participants continue at the target dose for eight additional days with mobile monitoring

8 days

Mobile assessments

Follow-up

Participants are monitored for short-term nicotine use behaviors via phone assessments

30 days

Phone assessments

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Varenicline Tartrate

Trial Overview The study tests whether Varenicline Tartrate helps reduce cravings in tobacco users compared to a placebo. It involves VR assessments of nicotine cues before and after taking the drug or placebo, followed by mobile check-ins and a final phone assessment after one month.

How Is the Trial Designed?

Group I: Varenicline Experimental Treatment 1 Intervention

Following the baseline assessment, participants randomized to receive varenicline will complete an 8-day titration period to achieve the target dose. Titration of varenicline will be as follows: 0.5 mg once daily for Days 1-3, 0.5 mg twice daily for Days 4-7, and 1 mg twice daily on Day 8. Participants then return to the lab on Day 9 (or Days 10, 11 if necessary) for testing at the target dosage (1 mg twice daily) and continue at that dose for eight additional days (Days 10-17) for mobile monitoring.

Group II: Placebo Placebo Group 1 Intervention

Following the baseline assessment, participants randomized to receive placebo pill will follow the same dosing schedule as the active arm. They will return to the lab on Day 9 (or Days 10, 11 if necessary) for testing and continue at that dosing schedule for eight additional days (Days 10-17) for mobile monitoring.

Varenicline Tartrate is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Chantix for:

• Smoking cessation

Approved in European Union as Champix for:

• Smoking cessation

Approved in Canada as Champix for:

• Smoking cessation

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

In a study of 12,159 patients, varenicline was associated with reported neuropsychiatric events, particularly anxiety, but no significant increase in these events was found over time, suggesting that the drug's safety profile remains largely stable.

While 7-17% of neuropsychiatric events were attributed to varenicline by general practitioners, the analysis did not raise significant safety concerns, indicating that further investigation is needed to clarify the relationship between varenicline and anxiety symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropsychiatric events with varenicline: a modified prescription-event monitoring study in general practice in England. Buggy, Y., Cornelius, V., Fogg, C., et al.[2021]

In a study of 2,682 patients using varenicline for smoking cessation, nausea and vomiting were the most common reasons for discontinuation and the most frequently reported adverse drug reactions, highlighting the need for patient monitoring regarding gastrointestinal side effects.

While some psychiatric events were reported, including anxiety and depression, all cases of suicidal behavior involved patients with prior psychiatric conditions, suggesting that clinicians should closely monitor individuals with such histories when prescribing varenicline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and drug utilization profile of varenicline as used in general practice in England: interim results from a prescription-event monitoring study. Kasliwal, R., Wilton, LV., Shakir, SA.[2021]

In a study of 50 veterans using varenicline for smoking cessation, only 30% successfully quit smoking, which is lower than the 44% success rate reported in premarketing studies.

The study found a significant association between underlying psychiatric disorders and treatment failure, with all patients who discontinued due to adverse drug events related to mood changes having a history of mental illness, highlighting the need for careful monitoring in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of varenicline in a veteran population with a high prevalence of mental illness. Purvis, TL., Mambourg, SE., Balvanz, TM., et al.[2015]

Varenicline, a medication used to help people quit smoking, is known to have some psychiatric and behavioral side effects, including reports of tardive dyskinesia, although these were not previously documented in literature.

This study presents the first two documented cases of withdrawal emergent dyskinesias associated with varenicline, highlighting a potential safety concern for users of the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Withdrawal-Emergent Dyskinesias following Varenicline Therapy. Toffey, BA., Rabin, M., Kurlan, R.[2020]

In a study of 70 patients with brain lesions, those who quit smoking after their injury (Quitters) did not show higher rates of depression compared to those who continued smoking (Non-Quitters), indicating that smoking cessation itself is not linked to increased depression in this population.

The findings suggest that the neuropsychiatric side effects associated with varenicline, such as depression, are likely due to the medication rather than the act of quitting smoking, as both groups exhibited similar levels of depression and related symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Smoking cessation after brain damage does not lead to increased depression: implications for understanding the psychiatric complications of varenicline. Tranel, D., McNutt, A., Bechara, A.[2021]

In a real-world study involving 566 participants across four European countries, varenicline was found to be an effective smoking cessation aid, with a 64.6% quit rate by the end of the 12-week treatment period.

The safety profile of varenicline was acceptable, with the most common side effects being mild to moderate nausea (8.9%) and insomnia (2.9%), and only 3.4% of participants discontinued due to treatment-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of varenicline as an aid to smoking cessation: results of an inter-European observational study. Boudrez, H., Gratziou, C., Messig, M., et al.[2015]

Varenicline, an FDA-approved medication for smoking cessation, significantly increases the chances of quitting smoking, with continuous abstinence rates 2.7 to 3.1 times higher than placebo over a 52-week period after 12 weeks of treatment.

In addition to helping smokers quit, varenicline reduces cravings and withdrawal symptoms, making it a valuable option for those looking to stop smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varenicline: a review of its use as an aid to smoking cessation therapy. Keating, GM., Siddiqui, MA.[2018]

In a review of ten randomized controlled trials involving 3091 participants, varenicline did not show a significant increase in overall psychiatric disorders compared to placebo, with an incidence of 10.7% in the varenicline group versus 9.7% in the placebo group.

While varenicline was associated with a higher incidence of sleep disorders, there were no reported cases of suicidal ideation or behavior in the analyzed studies, suggesting that varenicline is generally safe for smokers without current psychiatric conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychiatric adverse events in randomized, double-blind, placebo-controlled clinical trials of varenicline: a pooled analysis. Tonstad, S., Davies, S., Flammer, M., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4824380/

Varenicline for smoking cessation: a narrative review of ... Clinical trials have consistently demonstrated that varenicline is a safe and effective agent for smoking cessation.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9293179/

Comparative clinical effectiveness and safety of tobacco ... Most tobacco cessation monotherapies and combination therapies are more effective than placebo at helping participants to achieve sustained abstinence.

3. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2809121

Adaptive Smoking Cessation Using Precessation ... In this trial, the abstinence rate was 24% for adaptive treatment and 9% for standard treatment, with an absolute difference of 15.6 percentage ...

4. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2818356

Smoking Cessation After Initial Treatment Failure With ... On average, varenicline and combined nicotine replacement therapy (CNRT) appear to consistently produce the highest levels of long-term ...

5. hollingscancercenter.musc.edu hollingscancercenter.musc.edu/news/archive/2024/05/16/first-us-trial-of-varenicline-for-ecigarette-cessation-shows-positive-results

First US trial of varenicline for e-cigarette cessation shows ... “We had a 15% difference in quit rates, with those in the medication group having a quit rate of 45%,” said Lisa Fucito, Ph.D., lead author and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2962400/

Varenicline for smoking cessation: efficacy, safety, and ... After 52 weeks of follow-up, subjects receiving varenicline had significantly higher smoking abstinence rates compared with those receiving placebo (44% versus ...

7. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2820435

Varenicline and Nicotine Replacement Therapy for ... Varenicline is the most effective sole pharmacotherapy for smoking cessation and is as effective as combination nicotine replacement therapy ( ...

8. tobaccopreventioncessation.com tobaccopreventioncessation.com/Use-of-low-dose-varenicline-in-patients-who-do-not-tolerate-standard-dose-varenicline,194629,0,2.html

Use of low-dose varenicline in patients who do not tolerate ... The purpose of this study was to determine whether patients who previously discontinued standard-dose varenicline due to adverse events could tolerate and ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2589537023004935

Varenicline for smoking cessation in individuals who ... The findings of the study show the potential of varenicline in aiding these individuals in quitting smoking and achieving prolonged abstinence from tobacco ...